Recent studies have suggested that the Ah receptor plays a key role in regulating immune system function and in diseases of the immune system. Our studies have been designed to 1) evaluate the factors that govern expression of the Ah receptor in human lymphocytes, 2) evaluate the ability of dioxin (a known immunotoxin) to interact with the expressed receptor, and 3) to determine if this interaction produces changes in lymphocyte gene expression. We have found that expression of the Ah receptor is cell cycle dependent; resting leukocytes do not contain detectable amounts of Ah receptor whereas mitogen stimulation leads to rapid synthesis. Likewise, mitogen stimulation produces a dramatic increase in expression of dioxin responsive genes preceded by binding of dioxin to the Ah receptor. Current studies are quantifying dioxin responsive genes in lymphocyte samples from people exposed either occupationally or environmentally to dioxin. Preliminary data indicate marked interindividual variation in these molecular and biochemical changes. We have established collaborations to determine if sensitivity to the biochemical effects of dioxin is associated with corresponding sensitivities to cancer and immunological changes.